Safety of and Cellular Response to Segmental Bronchoprovocation in Allergic Asthma

Abstract

RationaleDespite its incorporation into research studies, the safety aspects of segmental allergen bronchoprovocation and differences in cellular response among different allergens have received limited consideration.MethodsWe performed 87 segmental challenges in 77 allergic asthma subjects. Allergen dose was based on each subject’s response to whole lung allergen challenge. Bronchoalveolar lavage was performed at 0 and 48 hours. Safety indicators included spirometry, oxygen saturation, heart rate, and symptoms.ResultsAmong subjects challenged with ragweed, cat dander, or house dust mite, there were no differences in safety indicators. Subjects demonstrated a modest oxygen desaturation and tachycardia during the procedure that returned to normal prior to discharge. We observed a modest reduction in forced vital capacity and forced expiratory volume in one second following bronchoscopy. The most common symptoms following the procedure were cough, sore throat and fatigue. Total bronchoalveolar lavage fluid cell numbers increased from 13±4 to 106±108×104 per milliliter and eosinophils increased from 1±2 to 44±20 percent, with no significant differences among the three allergens.ConclusionsIn mild allergic asthma, segmental allergen bronchoprovocation, using individualized doses of aeroallergens, was safe and yielded similar cellular responses.

Quantification of Pulmonary Inflammation after Segmental Allergen Challenge Using Turbo-Inversion Recovery-Magnitude Magnetic Resonance Imaging

“…There was a slight intermittent reduction in pulmonary function variables that was statistically significant in the asthma group but not in healthy subjects. The magnitude of deterioration was mild and in line with previous reports (28)(29)(30), although the number of challenged segments and therefore invasiveness was higher in our study.…”

Characterization of Siglec-8 Expression on Lavage Cells after Segmental Lung Allergen Challenge

“…To determine Siglec-8 expression on human airway cells, we first used 3-color flow cytometry similar to protocols we have used before and analyzed cells recovered by BAL 48 h after segmental lung allergen challenge of subjects with allergic asthma [20]. BAL cells were gated as shown in Figure 1.…”

“…In allergic human subjects, segmental bronchoprovocation with allergen is a model of allergic airway inflammation that induces intense local recruitment of inflammatory cells, including eosinophils and basophils [20]. We utilized this model to characterize Siglec-8 expression and localization on cells in bronchoalveolar lavage (BAL).…”

Human Airway Eosinophils Exhibit Preferential Reduction in STAT Signaling Capacity and Increased CISH Expression

“…Fluid from bronchoalveolar lavage (BAL) was recovered and EOS A were isolated 48 hours after segmental bronchoprovocation with allergen (SBP-Ag), where antigen dose for SBP defined and BAL performed as described (27, 36). In brief, EOS A were obtained after centrifuging BAL fluid through a Percoll bilayer (1.085/1.100 g/mL), with the recovered EOS population at the interface between the two layers.…”